title: Mes1 controls the meiosis I to meiosis II transition by distinctly regulating the anaphase-promoting complex/cyclosome coactivators Fzr1/Mfr1 and Slp1 in fission yeast.
abstract: Meiosis is a specialized form of cell division generating haploid gametes and is dependent upon protein ubiquitylation by the anaphase-promoting complex/cyclosome (APC/C). Accurate control of the APC/C during meiosis is important in all eukaryotic cells and is in part regulated by the association of coactivators and inhibitors. We previously showed that the fission yeast meiosis-specific protein Mes1 binds to a coactivator and inhibits APC/C; however, regulation of the Mes1-mediated APC/C inhibition remains elusive. Here we show how Mes1 distinctively regulates different forms of the APC/C. We study all the coactivators present in the yeast genome and find that only Slp1/Cdc20 is essential for meiosis I progression. However, Fzr1/Mfr1 is a critical target for Mes1 inhibition because fzr1Δ completely rescues the defect on the meiosis II entry in mes1Δ cells. Furthermore, cell-free studies suggest that Mes1 behaves as a pseudosubstrate for Fzr1/Mfr1 but works as a competitive substrate for Slp1. Intriguingly, mutations in the D-box or KEN-box of Mes1 increase its recognition as a substrate by Fzr1, but not by Slp1. Thus Mes1 interacts with two coactivators in a different way to control the activity of the APC/C required for the meiosis I/meiosis II transition.
authors.affiliation: Cell Cycle Control Group, UCL Cancer Institute, University College London, London WC1E6BT, United Kingdom.
authors.forename: Yuu
authors.initials: Y
authors.lastname: Kimata
authors.forename: Kenji
authors.initials: K
authors.lastname: Kitamura
authors.forename: Nicola
authors.initials: N
authors.lastname: Fenner
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Yamano
mesh_terms: D000705:Anaphase; D064173:Anaphase-Promoting Complex-Cyclosome; D064199:Cdc20 Proteins; D064200:Cdh1 Proteins; D018797:Cell Cycle Proteins / Q000378:metabolism*; D008540:Meiosis; D009154:Mutation / Q000235:genetics; D012568:Schizosaccharomyces / Q000166:cytology* / Q000235:genetics / Q000378:metabolism*; D029702:Schizosaccharomyces pombe Proteins / Q000235:genetics / Q000378:metabolism*; D043743:Ubiquitin-Protein Ligase Complexes / Q000378:metabolism; D054875:Ubiquitination
chemical_list: D064199:Cdc20 Proteins; D064200:Cdh1 Proteins; D018797:Cell Cycle Proteins; C432695:Mes1 protein, S pombe; D029702:Schizosaccharomyces pombe Proteins; C577587:mfr1 protein, S pombe; C577504:slp1 protein, S pombe; D043743:Ubiquitin-Protein Ligase Complexes; D064173:Anaphase-Promoting Complex-Cyclosome